title: Low pathogenic avian influenza A(H7N9) virus causes high mortality in ferrets upon intratracheal challenge: a model to study intervention strategies.
abstract: Infections with low pathogenic avian influenza (LPAI) A(H7N9) viruses have caused more than 100 hospitalized human cases of severe influenza in China since February 2013 with a case fatality rate exceeding 25%. Most of these human infections presented with severe viral pneumonia, while limited information is available currently on the occurrence of mild and subclinical cases. In the present study, a ferret model for this virus infection in humans is presented to evaluate the pathogenesis of the infection in a mammalian host, as ferrets have been shown to mimic the pathogenesis of human infection with influenza viruses most closely. Ferrets were inoculated intratracheally with increasing doses (>10 e5 TCID50) of H7N9 influenza virus A/Anhui/1/2013 and were monitored for clinical and virological parameters up to four days post infection. Virus replication was detected in the upper and lower respiratory tracts while animals developed fatal viral pneumonia. This study illustrates the high pathogenicity of LPAI-H7N9 virus for mammals. Furthermore, the intratracheal inoculation route in ferrets proofs to offer a solid model for LPAI-H7N9 virus induced pneumonia in humans. This model will facilitate the development and assessment of clinical intervention strategies for LPAI-H7N9 virus infection in humans, such as preventive vaccination and the use of antivirals.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: J H C M
authors.initials: JH
authors.lastname: Kreijtz
authors.forename: E J B Veldhuis
authors.initials: EJ
authors.lastname: Kroeze
authors.forename: K J
authors.initials: KJ
authors.lastname: Stittelaar
authors.forename: L
authors.initials: L
authors.lastname: de Waal
authors.forename: G
authors.initials: G
authors.lastname: van Amerongen
authors.forename: S
authors.initials: S
authors.lastname: van Trierum
authors.forename: P
authors.initials: P
authors.lastname: van Run
authors.forename: T
authors.initials: T
authors.lastname: Bestebroer
authors.lastname: T Kuiken
authors.forename: R A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: G F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: A D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000825:Animal Structures / Q000821:virology; D000818:Animals; D001717:Birds; D002681:China; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000401:mortality* / Q000473:pathology / Q000821:virology*; D012137:Respiratory System / Q000821:virology; D016019:Survival Analysis
keywords: Avian influenza A; H7N9; Intervention strategies